INCREASES IN PULSE PRESSURE IMPAIR ACETYLCHOLINE-INDUCED VASCULAR RELAXATION

Effects of pulse pressure on acetylcholine-induced endothelium-depende nt relaxation were investigated using a cascade bioassay model. Intact carotid arteries from rabbits were perfused at constant flow, and act ivity of endothelium-derived relaxing factor (EDRF) was assayed by mea suring changes in isometric tension in a detector ring without endothe lium. When pulse pressure of the donor artery was raised from similar to 2 to 10 mmHg, relaxation to acetylcholine (10(-7) M) was reduced fr om 31 +/- 3 (means +/- SE) to 20 +/- 2% (expressed as percent relaxati on of phenylephrine-induced tone). Responses of the detector ring to n itroprusside were unchanged. Superoxide dismutase (SOD) and indomethac in each prevented impairment of relaxation to acetylcholine at high pu lse pressure. When the donor artery was perfused at a higher mean pres sure, elevation of pulse pressure also impaired relaxation to acetylch oline, and this impairment was prevented by SOD. These findings sugges t that elevation of pulse pressure inhibits acetylcholine-induced, end othelium-dependent relaxation, and this inhibitory effect is mediated by generation of oxygen radicals.